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European Heart Journal Advance Access originally published online on April 8, 2005
European Heart Journal 2005 26(17):1783-1789; doi:10.1093/eurheartj/ehi237
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org

C-reactive protein in the prediction of cardiovascular and overall mortality in middle-aged men: a population-based cohort study

David E. Laaksonen1,2,*, Leo Niskanen1, Kristiina Nyyssönen3, Kari Punnonen4, Tomi-Pekka Tuomainen3 and Jukka T. Salonen3,5,6

1Department of Medicine, Kuopio University Hospital, PO Box 1777, FIN-70211 Kuopio, Finland
2Department of Physiology, University of Kuopio, Kuopio, Finland
3Research Institute of Public Health, University of Kuopio, Kuopio, Finland
4Department of Clinical Chemistry, Kuopio University Hospital, PO Box 1777, FIN-70211 Kuopio, Finland
5Department of Public Health and General Practice, University of Kuopio, Kuopio, Finland
6Oy Jurilab Ltd, Kuopio, Finland

Received 17 October 2004; revised 13 February 2005; accepted 23 February 2005; online publish-ahead-of-print 8 April 2005.

* Corresponding author. Tel: +358 17 173 311; fax: +358 17 163 112. E-mail address: david.laaksonen{at}uku.fi

Aims Cut-offs for C-reactive protein concentrations have been recommended for risk stratification, but little is known about how these cut-offs predict cardiovascular risk in population-based cohorts. We therefore assessed the association of C-reactive protein levels with cardiovascular mortality in a population-based cohort of 2321 middle-aged men stratified by the presence of cardiovascular disease (CVD) at baseline.

Methods and results C-reactive protein concentrations were categorized according to current recommendations (1 and 3 mg/L). During the 15 year follow-up, 77 men without CVD and 121 men with CVD at baseline died of CVD. In men without CVD at baseline (n=1476), age-adjusted cardiovascular mortality was 4.1-fold higher (95% CI 2.1–8.2) for C-reactive protein levels between 3.0 and 9.9 mg/L at baseline than for C-reactive protein levels <1.0 mg/L. In men with CVD at baseline (n=845), the corresponding age-adjusted cardiovascular mortality was 3.3-fold higher (95% CI 2.0–5.3). Adjustment for conventional CVD risk factors attenuated the risk somewhat. Further adjustment for dietary and lifestyle factors and factors related to insulin resistance did not affect the association. Classification of C-reactive protein by tertiles gave qualitatively similar results, but identified twice as many men at high risk. C-reactive protein levels also predicted overall mortality.

Conclusion Currently, recommended cut-offs for C-reactive protein levels identify men at risk for cardiovascular and overall death independently of conventional and other risk factors in a population-based sample of middle-aged men with and without CVD at baseline. Lower cut-offs may better identify men at high risk for cardiovascular death, but improvement of current recommendations will require standardization of C-reactive protein assays.

Key Words: Inflammation • C-reactive protein • Cardiovascular disease • Risk factors • Mortality • Cohort study


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